The nature of the interaction between the copper ion and the protein moiety in copper proteins is not understood. In the blue protein, or azurin, from Pseudomonas aeruginosa, the copper atom is assumed to be imbedded within the hydrophobic core of the protein, but with the possible exception of a cysteine sulfhydryl group, no protein-donated ligands to the copper atom have been clearly identified. Chemical modification of the protein offers a good probe of the protein structure which should aid in understanding this structure and the nature of the protein-cofactor interaction. Emphasis is to be placed on the selective modification of amino acid side chains that could potentially provide ligands for the copper atom, and these modifications will be performed on both the native protein and the metal-free derivative. The effects of the changes in structure brought about by chemical modification will also be assessed by analyzing changes in the function of the protein, namely the transfer of electrons. Kinetic analysis of the electron-transfer activity of the protein and its modified derivatives toward other electron transfer as well as toward small chemical oxidizing and reducing agents will be performed. The primary aims are to understand more clearly the nature of protein-metal interaction and the protein-protein interactions involved in the electron-transfer activity.